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1.  Safety and reactogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 viral-like-particle vaccine in older adolescents and young adults 
Human Vaccines  2011;7(7):768-775.
Prophylactic vaccination with a quadrivalent HPV (types 6, 11, 16, 18) vaccine (qHPV) has been shown to prevent infection with HPV 6/11/16/18 and associated disease in women and more recently, in men. Here we report on the safety and reactogenicity of the qHPV vaccine in males. A total of 4,065 healthy males aged 16–26 years were enrolled into a randomized, placebo-controlled, double-blind trial. Subjects were randomized 1:1 to receive qHPV vaccine or placebo at day 1, month 2 and month 6. Safety and tolerability were assessed via the collection of reported adverse experiences (AEs). All serious AEs (vaccine- or procedure-related or not) and all deaths occurring during the study were recorded. Safety analyses were conducted in all subjects who received at least one dose of vaccine or placebo. The proportion of subjects who reported at least one injection-site AE was higher in the qHPV vaccine group versus the placebo group (60.1% vs. 53.7%, respectively), however most of these AEs were mild/moderate in intensity. The incidence of at least one systemic AE was comparable between the vaccine and placebo groups (31.7% vs. 31.4%, respectively). There were no vaccine-related serious AEs or deaths. The occurrence of AEs did not increase with each successive injection, and among trial participants who were seropositive for at least one vaccine HPV type at enrollment, the profile of adverse events was similar to that of the entire study cohort. The qHPV vaccine was generally well tolerated in males aged 16–26 years and had a favorable safety profile.
PMCID: PMC3219080  PMID: 21712645
human papillomavirus (HPV); vaccine; safety; male; adult; adolescent
2.  Baroreflex deficiency induces additional impairment of vagal tone, diastolic function and calcium handling proteins after myocardial infarction 
Baroreflex dysfunction has been considered an important mortality predictor after myocardial infarction (MI). However, the impact of baroreflex deficiency prior to MI on tonic autonomic control and cardiac function, and on the profile of proteins associated with intracellular calcium handling has not yet been studied. The aim of the present study was to analyze how the impairment of baroreflex induced by sinoaortic denervation (SAD) prior to MI in rats affects the tonic autonomic control, ventricular function and cardiomyocyte calcium handling proteins. After 15 days of following or SAD surgery, rats underwent MI. Echocardiographic, hemodynamic, autonomic and molecular evaluations were performed 90 days after MI. Baroreflex impairment led to additional damage on: left ventricular remodeling, diastolic function, vagal tonus and intrinsic heart rate after MI. The loss of vagal component of the arterial baroreflex and vagal tonus were correlated with changes in the cardiac proteins involved in intracellular calcium homeostasis. Furthermore, additional increase in sodium calcium exchanger expression levels was associated with impaired diastolic function in experimental animals. Our findings strongly suggest that previous arterial baroreflex deficiency may induce additional impairment of vagal tonus, which was associated with calcium handling proteins abnormalities, probably triggering ventricular diastolic dysfunction after MI in rats.
PMCID: PMC4058313  PMID: 24936224
Arterial baroreflex; myocardial infarction; autonomic tone; cardiac function; cardiac remodeling; calcium handling proteins
3.  Effect of simvastatin in the autonomic system is dependent on the increased gain/sensitivity of the baroreceptors 
Physiological Reports  2013;1(3):e00045.
A number of mechanisms have been proposed to explain the pleiotropic effect of statin therapy to reduce sympathetic outflow in cardiovascular disease. We tested the hypothesis that statin treatment could improve baroreflex gain-sensitivity triggered by morphological adaptations in the mechanoreceptor site, thus reducing sympathetic activity, regardless of arterial pressure (AP) level reduction. Male spontaneously hypertensive rats (SHR) were divided into control (SHR, n = 8) and SHR-simvastatin (5 mg/kg/day, for 7 days) (SHR-S, n = 8). After treatment, AP, baroreflex sensitivity (BRS) in response to AP-induced changes, aortic depressor nerve activity, and spectral analyses of pulse interval (PI) and AP variabilities were performed. Internal and external carotids were prepared for morphoquantitative evaluation. Although AP was similar between groups, sympathetic modulation, represented by the low frequency band of PI (SHR: 6.84 ± 3.19 vs. SHR-S: 2.41 ± 0.96 msec2) and from systolic AP variability (SHR: 3.95 ± 0.36 vs. SHR-S: 2.86 ± 0.18 mmHg2), were reduced in treated animals. In parallel, simvastatin induced an increase of 26% and 21% in the number of elastic lamellae as well as a decrease of 9% and 25% in the carotid thickness in both, external and internal carotid, respectively. Moreover, improved baroreceptor function (SHR: 0.78 ± 0.03 vs. SHR-S: 1.06 ± 0.04% mv/mmHg) was observed in addition to a 115% increase in aortic depressor nerve activity in SHR-S rats. Therefore, our data suggest that the reduction of sympathetic outflow in hypertension by simvastatin treatment may be triggered by structural changes in the carotid arteries and increased BRS in response to an improvement of the baroreceptors discharge and consequently of the afferent pathway of the baroreflex arch.
PMCID: PMC3835001  PMID: 24303130
Baroreceptor function; baroreflex sensitivity; Hypertension; statins; sympathetic modulation
4.  Characterization of Novel Leishmania infantum Recombinant Proteins Encoded by Genes from Five Families with Distinct Capacities for Serodiagnosis of Canine and Human Visceral Leishmaniasis 
To expand the available panel of recombinant proteins that can be useful for identifying Leishmania-infected dogs and for diagnosing human visceral leishmaniasis (VL), we selected recombinant antigens from L. infantum, cDNA, and genomic libraries by using pools of serum samples from infected dogs and humans. The selected DNA fragments encoded homologs of a cytoplasmic heat-shock protein 70, a kinesin, a polyubiquitin, and two novel hypothetical proteins. Histidine-tagged recombinant proteins were produced after subcloning these DNA fragments and evaluated by using an enzyme-linked immunosorbent assays with panels of canine and human serum samples. The enzyme-linked immunosorbent assays with different recombinant proteins had different sensitivities (67.4–93.0% and 36.4–97.2%) and specificities (76.1–100% and 90.4–97.3%) when tested with serum samples from Leishmania-infected dogs and human patients with VL. Overall, no single recombinant antigen was sufficient to serodiagnosis all canine or human VL cases.
PMCID: PMC3225146  PMID: 22144438
5.  Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in Males 
The New England journal of medicine  2011;364(5):401-411.
Infection with human papillomavirus (HPV) and diseases caused by HPV are common in boys and men. We report on the safety of a quadrivalent vaccine (active against HPV types 6, 11, 16, and 18) and on its efficacy in preventing the development of external genital lesions and anogenital HPV infection in boys and men.
We enrolled 4065 healthy boys and men 16 to 26 years of age, from 18 countries in a randomized, placebo-controlled, double-blind trial. The primary efficacy objective was to show that the quadrivalent HPV vaccine reduced the incidence of external genital lesions related to HPV-6, 11, 16, or 18. Efficacy analyses were conducted in a per-protocol population, in which subjects received all three vaccinations and were negative for relevant HPV types at enrollment, and in an intention-to-treat population, in which subjects received vaccine or placebo, regardless of baseline HPV status.
In the intention-to-treat population, 36 external genital lesions were seen in the vaccine group as compared with 89 in the placebo group, for an observed efficacy of 60.2% (95% confidence interval [CI], 40.8 to 73.8); the efficacy was 65.5% (95% CI, 45.8 to 78.6) for lesions related to HPV-6, 11, 16, or 18. In the per-protocol population, efficacy against lesions related to HPV-6, 11, 16, or 18 was 90.4% (95% CI, 69.2 to 98.1). Efficacy with respect to persistent infection with HPV-6, 11, 16, or 18 and detection of related DNA at any time was 47.8% (95% CI, 36.0 to 57.6) and 27.1% (95% CI, 16.6 to 36.3), respectively, in the intention-to-treat population and 85.6% (97.5% CI, 73.4 to 92.9) and 44.7% (95% CI, 31.5 to 55.6) in the per-protocol population. Injection-site pain was significantly more frequent among subjects receiving quadrivalent HPV vaccine than among those receiving placebo (57% vs. 51%, P<0.001).
Quadrivalent HPV vaccine prevents infection with HPV-6, 11, 16, and 18 and the development of related external genital lesions in males 16 to 26 years of age. (Funded by Merck and others; number, NCT00090285.)
PMCID: PMC3495065  PMID: 21288094
6.  Immunogenicity of the Quadrivalent Human Papillomavirus (Type 6/11/16/18) Vaccine in Males 16 to 26 Years Old 
Human papillomavirus (HPV) infection can lead to significant disease in males, including anogenital warts, intraepithelial neoplasias, and several types of oral and anogenital cancers. The quadrivalent HPV (type 6/11/16/18) L1 virus-like particle (VLP) vaccine (qHPV vaccine; Gardasil) has recently been demonstrated to prevent persistent infection and associated disease related to vaccine HPV types in males. We report the overall immunogenicity results from a trial of the quadrivalent HPV vaccine in males. Overall, 3,463 heterosexual men and 602 men who had sex with men were enrolled into a randomized, placebo-controlled, double-blind safety, immunogenicity, and efficacy study. Serum samples were collected prior to vaccination at day 1 and at months 7, 24, and 36 postvaccination. Immunogenicity was evaluated with a multiplex, competitive Luminex immunoassay. Almost all subjects (97.4 to 99.2%) seroconverted for vaccine HPV types by month 7. At month 36, 88.9%, 94.0%, 97.9%, and 57.0% of subjects were still seropositive for HPV-6, -11, -16, and -18, respectively. For all vaccine HPV types, black subjects had significantly higher antibody titers at month 7 than did both Caucasian and Asian subjects. An anamnestic antibody response was seen in men seropositive before vaccination. The vaccine was highly immunogenic in males 16 to 23 years of age; responses were comparable to those observed in women. Furthermore, the immune responses were consistent with the established efficacy of the vaccine in the prevention of incident and persistent HPV infection, anogenital warts, and anal intraepithelial neoplasia.
PMCID: PMC3272915  PMID: 22155768
7.  External Genital Human Papillomavirus Prevalence and Associated Factors Among Heterosexual Men on 5 Continents 
Background. We examined the baseline prevalence of penile, scrotal, and perineal/perianal human papillomavirus (HPV) in heterosexual men (HM). We also evaluated baseline characteristics of HM to assess factors associated with prevalent HPV detection.
Methods. We tested serum samples from 3463 HM aged 16–24 years with 1–5 lifetime female sexual partners for antibodies to HPV 6, 11, 16, and 18. We collected baseline swab specimens for the detection of DNA of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59 from 3 areas: penile, scrotal, and perineal/perianal. Risk factors for prevalent HPV DNA detection were evaluated.
Results. The prevalence of any tested HPV type was 18.7% at the penis, 13.1% at the scrotum, 7.9% at the perineal/perianal region, and 21.0% at any site. Having >3 lifetime female sexual partners had the greatest impact on HPV prevalence: odds ratio (OR) 3.2 (95% confidence interval (CI) 2.1–4.9) for HPV 6, 11, 16, and 18; and OR 4.5 (95% CI 3.3–6.1) for all HPV types tested. HPV DNA detection was highest in Africa. Neither condom usage nor circumcision was associated with HPV DNA prevalence.
Conclusion. Genital-HPV DNA detection is common in young, sexually active HM. We found HPV to be most prevalent in African men and least prevalent in men from the Asia-Pacific region. Increased numbers of sexual partners was an important risk factor for HPV DNA prevalence.
PMCID: PMC3086430  PMID: 21148497
8.  Prevalence of and Risk Factors for Human Papillomavirus (HPV) Infection Among HIV-Seronegative Men Who Have Sex With Men 
Background. We examined the baseline prevalence of penile, scrotal, perineal/perianal, and intra-anal human papillomavirus (HPV) infection in human immunodeficiency virus (HIV)–seronegative men who have sex with men (MSM).
Methods. Data were analyzed from 602 MSM aged 16–27 years with ≤5 lifetime sexual partners. Serum samples were tested for antibodies to HPV6/11/16/18. Swab samples were collected separately from several anogenital areas for detection of HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59 DNA.
Results. The prevalence of any tested HPV type was 18.5% at the penis, 17.1% at the scrotum, 33.0% at the perineal/perianal region, 42.4% in the anal canal, and 48.0% at any site. Overall, 415 MSM (69.7%) were negative to HPV 6, 11, 16, and 18 at enrollment by both serology and DNA detection. Men residing in Europe and Latin America had significantly increased risk of HPV infection at external genital sites and the anal canal compared to men from Australia. Tobacco use and greater number of lifetime sexual partners was associated with higher HPV infection prevalence.
Conclusions. The prevalence of HPV infection is high among young sexually active MSM, with the anal canal being the most common site of infection. Lifetime number of sexual partners was the most important modifiable risk factor for anogenital HPV infection.
PMCID: PMC3086446  PMID: 21148498

Results 1-8 (8)